7-82005506-GAAAA-GAAAAA

Position:

• chr7-82005506-GAAAA-GAAAAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_000722.4(CACNA2D1):​c.1516-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 1,135,952 control chromosomes in the GnomAD database, including 79 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.030 (77 hom., cov: 31)
  • Exomes 𝑓: 0.064 (2 hom.)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Benign no assertion criteria provided B:3
• Conservation: PhyloP100: 0.00

Genes affected

CACNA2D1 (HGNC:1399): (calcium voltage-gated channel auxiliary subunit alpha2delta 1) The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion. [provided by RefSeq, Nov 2014]

CACNA2D1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 7-82005506-G-GA is Benign according to our data. Variant chr7-82005506-G-GA is described in ClinVar as [Benign]. Clinvar id is 1284308.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.1516-10dupT		intron_variant		ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.1516-10dupT		intron_variant		1	NM_000722.4	ENSP00000349320.3

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 2720 AN: 91524 Hom.: 77 Cov.: 31

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.0771

Gnomad AMR AF: 0.00967

Gnomad ASJ AF: 0.00196

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00181

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.0247

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0644 AC: 67209 AN: 1044378 Hom.: 2 Cov.: 0 AF XY: 0.0607 AC XY: 31834 AN XY: 524122

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0387

Gnomad4 ASJ exome AF: 0.0417

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.0380

Gnomad4 FIN exome AF: 0.0251

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.0605

GnomAD4 genome AF: 0.0298 AC: 2728 AN: 91574 Hom.: 77 Cov.: 31 AF XY: 0.0297 AC XY: 1310 AN XY: 44174

Gnomad4 AFR AF: 0.0932

Gnomad4 AMR AF: 0.00966

Gnomad4 ASJ AF: 0.00196

Gnomad4 EAS AF: 0.00101

Gnomad4 SAS AF: 0.00182

Gnomad4 FIN AF: 0.00529

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.0213

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs576139922; hg19: chr7-81634822;